Activation of protein kinase Cα inhibits insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1

Janice E. Chin, Feng Liu, Richard A. Roth

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82 Scopus citations


Chinese hamster ovary (CHO) cells were transfected with a cDNA encoding protein kinase Cα (PKC) and a cell line (CHO-PKCα) expressing approximately 7-fold greater amounts of PKC as the parental cells were isolated. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate in the CHO-PKCα cells inhibited by approximately 75% the: 1) insulin-stimulated increase in antiphosphotyrosine precipitable phosphatidylinositol 3-kinase activity in these cells; 2) insulin-stimulated increase in PI 3-kinase activity associated with insulin receptor substrate-1; and 3) tyrosine phosphorylation of the endogenous substrate, insulin receptor substrate-1. In contrast, 12-O-tetradecanoylphorbol-13-acetate treatment did not inhibit any of these responses in the parental CHO cells. These results indicate that excessive PKC activity can interfere in a very early step in insulin receptor signaling and are consistent with the hypothesis that excessive PKC activity may contribute to some states of insulin resistance.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalMolecular Endocrinology
Issue number1
StatePublished - Jan 1994


ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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